The most common inherited disorder causing blindness in man is retinitis pigmentosa, a disease or family of diseases in which the rod photoreceptors of the retina break down slowly and progressively over a period of years, and pigment epithelial cells move into the degenerating retina. Similar inherited diseases are known in dogs, mice, and rats. In an earlier study we showed that of these several animal models, the rat disease most closely matches the human disorder, in the sense that normal visual function develops early in life, and then the disease progresses steadily during "adolescence" until the rats become blind. Now we are finding strong evidence for the existence of a hitherto undescribed genetic factor that delays the onset of the disease into adult life and then slows its rate of progression so that the clinical and pathological picture becomes very similar indeed to the human disorder. We propose to complete the formal genetic analysis so as to define the mode of inheritance and provide inbred stocks with different rates of disease. Also we will use electron microscopic, autoradiographic, tissue culture, chemical, immunological, and behavioral methods to analyze how the mutant genes cause the retinal rod cells to degenerate. We also seek ways to slow down the rat disorder even further, or prevent its expression entirely, in the hope that we might be able to suggest possible therapy of its important human counterpart, retinitis pigmentosa.